Researchers here use data on cholesterol and health assessed in a large patient population over a 40 year period in order to determine how the risk of suffering atherosclerosis by age 75 varies with cholesterol levels assessed in the 30s and 40s. It is no surprise that higher cholesterol levels mean a greater risk of atherosclerosis, the development of fatty lesions that narrow and weaken blood vessels. The condition is one in which the macrophage cells responsible for removing these unwanted lipids from blood vessel walls are made dysfunctional by rising levels of oxidized cholesterol. The more cholesterol in the blood stream, the more oxidized cholesterol, all other things being equal.
Using data for individuals without prevalent cardiovascular disease, we characterised the age-specific and sex-specific long-term association of non-HDL cholesterol with cardiovascular disease. On the basis of this association, we derived and validated a tool specific for age, sex, and cardiovascular risk factors to assess the individual long-term probability of cardiovascular disease by the age of 75 years associated with non-HDL cholesterol. Further, we modelled the potentially achievable long-term cardiovascular disease risk, assuming a 50% reduction of non-HDL cholesterol.
Considerable uncertainty exists about the extent to which slightly increased or apparently normal cholesterol concentrations affect lifetime cardiovascular risk and about which thresholds should be used to merit a treatment recommendation, particularly in young people. Our study extends current knowledge because it suggests that increasing concentrations of non-HDL cholesterol predict long-term cardiovascular risk, particularly in cases of modest increase at a young age.
Results showed a stepwise increase of cardiovascular disease events across increasing concentrations of non-HDL cholesterol. 30-year cardiovascular disease event rates were approximately three-to-four times higher in women and men in the highest non-HDL cholesterol category (≥5.7 mmol/L) than those in the lowest category (less than 2.6 mmol/L; 33.7% vs 7.7% in women and 43.6% vs 12.8% in men). To estimate the long-term probability of a cardiovascular disease event associated with non-HDL cholesterol, we established a model for cardiovascular disease risk up to the age of 75 years. For example, women with non-HDL cholesterol concentrations between 3.7 and 4.8 mmol/L, younger than 45 years, and with at least two additional cardiovascular risk factors had a 15.6% probability of experiencing a non-fatal or fatal cardiovascular disease event by the age of 75 years (28.8% in men with the same characteristics).
We calculated the optimally achievable risk reduction for cardiovascular disease by the age of 75 years assuming a 50% reduction of non-HDL cholesterol. In the population with non-HDL cholesterol of 3.7-4.8 mmol/L, younger than 45 years, and with at least two risk factors, the long-term risk of cardiovascular disease could hypothetically be reduced from 15.6% to 3.6% in women and from 28.8% to 6.4% in men. Absolute risk reductions of cardiovascular disease were more pronounced in individuals with two or more cardiovascular disease risk factors than in those with one or no risk factors, and in men than women.